Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.
Science. 2011 Oct 14;334(6053):252-5. doi: 10.1126/science.1208930. Epub 2011 Aug 25.
Uterine leiomyomas, or fibroids, are benign tumors that affect millions of women worldwide and that can cause considerable morbidity. To study the genetic basis of this tumor type, we examined 18 uterine leiomyomas derived from 17 different patients by exome sequencing and identified tumor-specific mutations in the mediator complex subunit 12 (MED12) gene in 10. Through analysis of 207 additional tumors, we determined that MED12 is altered in 70% (159 of 225) of tumors from a total of 80 patients. The Mediator complex is a 26-subunit transcriptional regulator that bridges DNA regulatory sequences to the RNA polymerase II initiation complex. All mutations resided in exon 2, suggesting that aberrant function of this region of MED12 contributes to tumorigenesis.
子宫肌瘤，又称纤维瘤，是一种良性肿瘤，影响着全球数以百万计的女性，并可能导致相当大的发病率。为了研究这种肿瘤类型的遗传基础，我们通过外显子组测序研究了来自 17 名不同患者的 18 个子宫肌瘤，并在 10 个肿瘤中发现了中介复合物亚基 12（MED12）基因的肿瘤特异性突变。通过对另外 207 个肿瘤的分析，我们确定在总共 80 名患者的 159 个肿瘤（70%）中存在 MED12 改变。中介复合物是一种由 26 个亚基组成的转录调节剂，它将 DNA 调节序列桥接到 RNA 聚合酶 II 起始复合物。所有的突变都位于外显子 2 中，这表明 MED12 这一区域的异常功能导致了肿瘤的发生。
